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Precise tracing of mitochondrial transfer between cancer and T cells at single cell resolution

Hongyi Zhang, Xuexin Yu, Jianfeng Ye, Anli Zhang and Bo Li

Poster # 17

Mitochondrion (MT) as the energy-producing organelle participates in most metabolic activities of mammalian cells. Unidirectional mitochondrial transfer from T cells to cancer cells was recently observed "metabolically empowering" cancer cells while "depleting immune cells", providing new insights into tumor-T cell interaction and immune evasion. Here, we leveraged the widely adopted single-cell RNA-seq technology and introduced MERCI, a statistical deconvolution method for tracing and quantifying the process of mitochondrial trafficking between cancer and T cells. MERCI was benchmarked using data generated from a coculture system of MT-labeled cancer and T cells to accurately predict the recipient cells and their mitochondrial compositions. Both MT tracing from genomics data and the performance of MERCI were independently validated using a cutting-edge single cell mitochondrial sequencing technology. Application of MERCI to single cell human cancer samples identified a novel MT transfer phenotype, with its signature genes involved in cytoskeleton remodeling, energy production and TNFα signaling pathways. Finally, MT transfer is associated with high cell cycle activity and poor clinical outcome in pan-cancer analysis through MERCI. In summary, MERCI enabled systematic investigation of a novel aspect of tumor-immune interaction and revealed MT-transfer related genes and pathways that may lead to new therapeutic opportunities.

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